Peroxyhydrolysis of nerve agent VX and model compounds and related nucleophilic reactions

The exceedingly toxic agent VX [O-ethyl S-(diisopropylaminoethyl) methylphosphonothioate], 1a, and the midly toxic model compound O,S-diethyl methylphosphonothioate, 1b, react with HO- to give parallel P–S and P–O bond cleavages; the P–O cleavage of VX produces relatively unreactive but very toxic anionic phosphonothioate. Peroxyhydrolysis of 1a,b with HO2- involves quantitative P–S cleavage at rates 30–40 times that with HO- giving the corresponding phosphonate and sulfonate ions and disulfide as nontoxic products. In reaction of 1b with HO2- in H218O, oxygen in these final products is not derived from water and HO2- exclusively displaces the thiolate ion at phosphorus. Reaction of 1b with HSO5- gives the same products, but via oxidatively promoted attack of H218O on phosphorus. Kinetic and isotopic labelling results on reactions of 1a,b and a range of related compounds with HO2-, HO- and RO- and an oximate ion are interpreted in terms of concerted SN2(P) reactions rather than stepwise reactions with formation of a trigonal bipyramidal (TBP) intermediate. Product selectivity depends on the relative basicities of the anionic nucleophile and the leaving anions.